Delphinidin-3-O-glucoside in vitro suppresses NF-κB and changes the secretome of mesenchymal stem cells affecting macrophage activation

Anthocyanins are polyphenols that are promising chemopreventive agents. They stand out for their anti-inflammatory properties, with specific modulatory actions on the immune system. Additionally, regarding the immune system, a group of cells identified as mesenchymal stem cells (MSCs) have been attracting attention, mainly because of their capacity to migrate to sites of inflammation and produce potent immunomodulatory effects. Considering the ability of these cells to act on the immune system, as well as the properties of anthocyanins, especially delphinidin, in modulating the immune system, the aim of this study was to investigate the effects of delphinidin in influencing some immunoregulatory properties of MSCs.

MSCs were cultivated in the presence of delphinidin 3-O-β-d-glycoside and cell viability, the cell cycle and the production of soluble factors (interleukin [IL]-1β, IL-6, IL-10, transforming growth factor [TGF]-β, prostaglandin E₂ [PGE₂] and nitric oxide [NO]) were evaluated, as was the expression of the transcription factors nuclear factor (NF)-κB and STAT3. Additionally, the effects of conditioned media from MSCs on macrophage activation were assessed.

Delphinidin at 50 µM does not affect cell viability. In association with lipopolysaccharide, delphinidin was able to induce MSC proliferation. Additionally, delphinidin modulated the MSC immune response, showing increased levels of anti-inflammatory cytokines such as IL-10 and TGF-β as well as lower expression of NF-κB. Furthermore, conditioned media from MSCs inhibited macrophage metabolism, reducing the production of IL-1β, IL-12, and TNF-α and increasing IL-10.

Overall, this work showed that delphinidin can modify the immunomodulatory properties of MSCs, increasing the IL-10 production by macrophages.